Sickle cell anemia (SCA) is a genetic, life-limiting disease in which chronic anemia, sickled red blood cells, and inflammation cause debilitating pain and fatigue, and long-term complications to bodily organs. As newer treatments extend survival, a greater focus on health promotion is critical. Exercise, an important component of health promotion, is challenging in SCA because of complications associated with chronic anemia. Whereas strenuous exercise is contraindicated because it can lead to painful vaso-occlusive crises, mild to moderate exercise is recommended. Yet individuals with SCA tend to be less active and fit than healthy peers; thus are at greater risk for poorer health outcomes including obesity and cardiovascular problems. The problem is that individuals with SCA have difficulty self-managing (monitoring and self-regulating) their exercise regimen because existing exercise guidelines focus only on how to avoid potential complications. There are no guidelines on how to safely and effectively improve fitness or exercise capacity. For example, individuals with SCA are instructed to stop exercising when they begin to feel fatigued as a way of avoiding strenuous exercise because, theoretically, fatigue indicates a transition in metabolic state from aerobic to anaerobic metabolism. Being in an anaerobic metabolic state for any length of time can lead to vaso-occlusive crises. However, what the perception of fatigue during exercise represents is unknown. Does perceived fatigue indicate an anaerobic state, deconditioning, an emotion, or a combination of these factors? There are other subjective responses that may be more useful for guiding exercise intensity. In healthy individuals, subjective responses to exercise (perceptions of what one feels [effort] and how one feels [affect]) in relation to metabolic state are used to guide exercise prescription. We will study how fatigue and these subjective responses to exercise align with metabolic state to determine the ideal subjective response/s to help guide the self-management of safe and efficacious exercise in adolescents and young adults (AYA) with SCA. The hypothesis is that perceived effort and affect may align more closely to metabolic state than perceived fatigue. To test this hypothesis, AYA with SCA will complete an exercise session that involves an incremental bicycle test to volitional exhaustion (until they feel they cannot continue). The biomarker of metabolic state will be gas exchange threshold. Subjective responses that will be measured are effort, affect, and fatigue. Subjective responses will be examined in relation to metabolic state. The long-term objectives are to identify improved approaches to self-managing safe exercise intensities that are both inexpensive and efficient, and that can be used in testing future exercise interventions for AYA with SCA. Also, long-term, the aim is to determine whether exercise can have short-term benefits, such as improving SCA pain and fatigue; and long-term benefits, such as delaying or decreasing cardiopulmonary complications. Improving self-management in chronic illness is in NINR's strategic plan. This study will lay the foundation for developing a program of health promotion research in individuals with SCA.